Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members
Merli, M.; Patriarca, M.; Loudianos, G.; Valente, C.; Riggio, O.; De Felice, G.; Petrucci, F.; Caroli, S.; Attili, A.F.
Italian Journal of Gastroenterology and Hepatology 30(3): 270-275
1998
ISSN/ISBN: 1125-8055 PMID: 9759594 Document Number: 489639
Background/Aims. An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described We report on the use of this method for the study of a family with two numbers affected by Wilson's disease. Subjects. The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low ceruloplasmin levels and Kayser-Fleischer ring. Methods. All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry Results. The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into ceruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism. Conclusions. The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect.